Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.     

不同机种军事飞行员运动心肺功能研究

目的了解不同机种军事飞行员运动心肺功能有无差异。方法飞行员分为高性能战斗机和普通战斗机两组,采用意大利COSMED运动心肺功能测试仪,选择自行车功率计运动方式,以25 W/min功率递增速率极量运动方案,进行运动心肺功能测试,比较两组运动心肺功能数据的主要指标。结果两组飞行员各207例完成运动心肺功能测试,两组的年龄、身高、体质量和体质量指数差异均无统计学意义(P均>0.05)。两组数据的主要指标中,除了峰值氧脉搏[高性能战斗机组(15.36±2.43)mL/bpm,普通战斗机组(14.95±2.13)mL/bpm]差异有统计学意义(P=0.038),其他差异均无统计学意义,而且各指标差异幅度均较小,高性能战斗机飞行员组的峰值氧脉搏高于普通战斗机组2.74%。结论综合比较,高性能战斗机和普通战斗机飞行员的运动心肺功能无明显差异,提示两组飞行员日常有氧运动训练效果一致,在转换飞行机种时,可以不受运动心肺功能的限制。     

二维斑点追踪显像技术评估窒息新生儿左心室纵向收缩功能与心肌损害的相关性

【摘要】目的 探讨二维斑点追踪显像技术(2D-STI)评估新生儿窒息合并心肌损害后左心室整体及局部心肌的纵向收缩功能在早期诊断窒息新生儿心肌损害中的临床价值。方法 选择2019年07月至2020年12月期间在右江民族医学院附属医院新生儿科住院的足月窒息新生儿61例，经临床确诊合并心肌损害，根据Apgar评分分为轻度组31例和重度组30例，选择同期住院出生的正常足月新生儿30例作为对照组。检测受检者的血清肌酸激酶同工酶（CK-MB）、肌钙蛋白（cTnT）、左室舒张期前后径（LVDId）、左室射血分数（LVEF）、左室短轴缩短率（LVFS）、辛普森法左室射血分数（Simpson EF）、左室三腔心整体应变（GLS-LAX）、左室四腔心整体应变（GLS-A4C）、左室两腔心整体应变（GLS-A2C）、左室整体应变（GLS-AVG）,分析GLS-AVG和CK-MB、cTnT三者的相关性。结果 三组间CK-MB和cTnT比较差异有统计学意义（P<0.05）。三组间性别、体重、胎龄均无统计学差异（P>0.05）。三组间LVDId、LVEF、LVFS、Simpson EF比较差异无统计学意义（P>0.05）。GLS-AVG与CK-MB呈负性相关（r=-0.515，P=0.000），GLS-AVG与cTnT呈负性相关（r=-0.912，P=0.000）。结论 GLS-AVG与CK-MB、cTnT具有相关性，GLS-AVG可作为窒息新生儿心肌损害早期诊断指标。     

注意缺陷多动障碍儿童执行功能的评估与干预

ADHD儿童认知障碍的主要特征之一是执行功能损害,涉及包括前额叶皮层在内的特定脑区域及多层级脑网络异常。执行功能按照功能性分为冷-热两方面:冷执行功能损害主要表现于反应抑制、工作记忆以及认知灵活性等;热执行功能损害通常涉及延迟满足、赏罚相关决策、自我调节及情绪调节等。ADHD儿童的执行功能评估应基于可信范式进行文化适应性调整。临床干预不能单一聚焦于冷执行功能,需关注儿童的身体发育以及热执行功能(情绪社会方面)的发展进程,结合其他共病与心理状况,进行全面的动态随访与干预,以达到最佳的长期疗效。     

The role of dark adaptation in understanding early AMD

The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD.Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time.Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.     

新化合物Elixir-X对肝切及辐射所致衰老小鼠的抗衰老作用

目的 探讨蜂巢提取物Elixir-X对自然衰老及辐射衰老小鼠的影响，为Elixir-X的进一步研发提供药理学基础。方法 采用小鼠肝脏切除术建立自然衰老小鼠模型，将其分为空白对照组、Elixir-X组、白藜芦醇组及模型组，连续给药7 d后，检测小鼠70%肝脏切除后的再生过程中，衰老细胞、肝脏功能恢复与肝脏再生的变化，观察Elixir-X对自然衰老的影响；采用60CO辐射法建立辐射衰老小鼠模型，将其分为模型组、空白对照组、白藜芦醇组、Elixir-X高、低剂量组，通过检测小鼠肠隐窝干细胞再生、小肠绒毛结构以及衰老细胞的变化，对比不同剂量Elixir-X对辐射后衰老的影响。结果 在肝脏切除术的小鼠模型中，Elixir-X组的肝功能水平明显低于模型组的肝脏自然再生小鼠，显著促进了肝功能恢复（P＜0.05）；同时与模型组相比，Elixir-X组清除了肝脏切除后再生过程中产生的衰老细胞（P＜0.05），Ki-67的着色斑块明显增加，促进肝脏的再生，且肝血窦的扫描电镜影像结果中Elixir-X组肝血窦再生加快。60CO辐照小鼠模型中，与模型组相比，Elixir-X组有效促进辐照后肝脏功能恢复（P＜0.05），Elixir-X高剂量组体重也恢复到正常水平，与空白对照组无显著差异；与模型组相比，Elixir-X低剂量组小肠的β-Gal着色细胞减少，Elixir-X高剂量组甚至能更有效地减少衰老细胞（P＜0.05）；小肠HE染色的结果中，Elixir-X组小肠绒毛结构得到恢复；Ki-67的IHC染色中，与模型组相比，Elixir-X组着色板块更多，且着色区域都在肠隐窝干细胞位置。结论 Elixir-X能有效清除肝脏切除术引起的自然衰老与辐射引起的损伤性衰老细胞，对衰老具有显著地抑制作用。     

基于网络药理学和分子对接技术分析筒鞘蛇菰多糖治疗肝损伤的作用机制及体内实验研究＊

目的 基于网络药理学探讨并分析筒鞘蛇菰（Balanophora involucrata Hook. f.，BIH）治疗肝损伤的作用及分子机制，并通过大鼠体内实验验证相关预测靶点及筒鞘蛇菰提取物-蛇菰多糖（Polysaccharides of Balanophora involucrata Hook. f.，BPS）对实验性肝损伤的保护作用。方法 化学专业数据库、TCMID和TCMSP平台检索筒鞘蛇菰组成的化合物及可能靶点，以肝损伤为关键词检索GeneCards和网站，获得相关靶点，绘制Venn图，选交集靶点，将“化合物-靶点和疾病-靶点”关系导入Cytoscape V3.7.2软件，获得化合物-靶点-疾病的三重网络，对化合物及相关靶点蛋白行分子对接，并用交集靶点绘制蛋白互作网络图及进行GO生物功能和KEGG信号途径富集分析。结果 筒鞘蛇菰主要成分有11个化合物，其中与肝损伤有37个交集靶点，高度关联靶点包括NOS3、ESR1、TNF、MAOA、PTGS2、IL10等，GO和KEGG富集分析发现筒鞘蛇菰治疗肝损伤的分子机制，可能与调节肾上腺素能信号通路、cGMP-PKG信号及神经活性配体-受体交互通路等有关，而且ADRA1B、ADRA2A、ADRA2C、ADRB1/2等基因高度富集于这些通路中。动物体内实验发现BPS灌胃处理可减轻肝组织损伤、调控血清炎症因子肿瘤坏死因子α（Tumor necrosis factor， TNF-α）和白细胞介素10（IL-10）水平、提高抗氧化酶超氧化物歧化酶（superoxide dismutase，SOD）活性，并增强肝组织内氧化应激相关蛋白核因子E2相关因子2（NF-E2-related factor 2，NRF2）和醌NADH脱氢酶1（NQO1）的表达，从而抑制大鼠体内氧化应激损伤、减轻炎症反应和细胞凋亡，达到保护实验性肝损伤的作用。结论 本研究初步确定筒鞘蛇菰治疗肝损伤的有效成分、“化合物-蛋白-靶点”关联网络及发挥作用的分子机制，并通过动物体内实验证实蛇菰多糖保护肝损伤的机制与上调NRF2/NQO1通路来减轻氧化应激反应性损伤、减轻肝细胞凋亡有关。     

Long-term survival and postoperative complications of pre-liver transplantation transarterial chemoembolisation in hepatocellular carcinoma: A systematic review and meta-analysis

ObjectivesThe aim of this meta-analysis was to conduct a contemporary systematic review of high quality non-randomised controlled trials to determine the effect of pre-liver transplantation (LT) transarterial chemoembolisation (TACE) on long-term survival and complications of hepatocellular carcinoma (HCC) patients.BackgroundTACE is used as a neoadjuvant therapy to mitigate waitlist drop-out for patients with HCC awaiting LT. Previous studies have conflicting conclusions on the effect of TACE on long-term survival and complications of HCC patients undergoing LT.MethodsCINAHL, Cochrane Controlled Register of Trials, Embase, PubMed, and Web of Science were systematically searched. Baseline characteristics included number of patients outside Milan criteria, tumour diameter, MELD score, and time on the waiting list. Primary outcomes included 3- and 5-year overall and disease-free survival. Secondary outcomes included tumour recurrence, 30-day postoperative mortality, and hepatic artery and biliary complications.ResultsTwenty-one high-quality NRCTs representing 8242 patients were included. Tumour diameter was significantly larger in TACE patients (3.49 cm vs 3.15 cm, P = 0.02) and time on the waiting list was significantly longer in TACE patients (4.87 months vs 3.46 months, P = 0.05), while MELD score was significantly higher in non-TACE patients (10.81 vs 12.35, P = 0.005). All primary and secondary outcomes displayed non-significant differences.ConclusionPatients treated with TACE had similar survival and postoperative outcomes to non-TACE patients, however, they had worse prognostic features compared to non-TACE patients. These findings strongly support the current US and European clinical practice guidelines that neoadjuvant TACE can be used for patients with longer expected waiting list times (specifically >6 months). Randomised controlled trials would be needed to increase the quality of evidence.